Imaging herpes viral thymidine kinase-1 reporter gene expression with a new 18F-labeled probe: 2′-fluoro-2′-deoxy-5-[ 18F]fluoroethyl-1-β-d-arabinofuranosyl uracil Journal Article
| Authors: | Balatoni, J. A.; Doubrovin, M.; Ageyeva, L.; Pillarsetty, N.; Finn, R. D.; Gelovani, J. G.; Blasberg, R. G. |
| Article Title: | Imaging herpes viral thymidine kinase-1 reporter gene expression with a new 18F-labeled probe: 2′-fluoro-2′-deoxy-5-[ 18F]fluoroethyl-1-β-d-arabinofuranosyl uracil |
| Abstract: | The preparation and radiolabeling of 2′-fluoro-2′-deoxy-1- β-d-arabinofuranosyl-5-(2-fluoroethyl)-uracil (FFEAU) with 18F and its evaluation as a probe for imaging herpes simplex virus 1 thymidine kinase (HSV1-tk) gene expression are described. 2′-Fluoro-2′-deoxy- 3′,5′-di-O-benzoyl-1-β-d-arabinofuranosyl-3-N-benzoyl-5-(2- [18F]fluoroethyl)-uracil 12 was prepared by nucleophilic substitution of the corresponding tosyl 8 or trifluoroethanesulfonyl 9 derivative with n-Bu4N[18F]F. Base hydrolysis was used to remove the benzoyl protecting groups, followed by HPLC purification, to afford [ 18F]FFEAU 13. The trifluoroethanesulfonyl substrate 9 appears to be the better labeling precursor. Carrier n-Bu4NF was added to the labeling reaction, which resulted in specific activities of 40-70 Ci/mmol (estimated). Radiochemical purity averaged 94±4%. Although [ 18F]FFEAU was obtained in low radiochemical yield with 9 and further optimization of the radiosynthesis will be required, sufficient product was available for a series of in vitro and in vivo studies. [18F]FFEAU was directly compared with [3H]TdR in a series of in vitro accumulation studies involving a HSV1-tk stably transduced cell line, RG2TK+ and a nontransduced, wild-type RG2 cells. The initial in vitro and in vivo imaging studies are promising; FFEAU has in vitro accumulation and sensitivity characteristics similar to that previously reported for FIAU, but greater selectivity than FIAU due to lower uptake and retention in nontransduced cells and tissues. The animal imaging experiment showed low levels of radioactivity in the lungs, with little or no radioactivity seen in the heart, liver, spleen and intestines. © 2005 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; nonhuman; radiopharmaceuticals; animals; animal tissue; gene expression; gene expression profiling; spleen; cell line; animal experiment; cell line, tumor; transfection; wild type; imaging system; liver; tissue distribution; glioblastoma; rat; radioactivity; lung; radiopharmaceutical agent; arabinofuranosyluracil; reporter gene; metabolic clearance rate; thymidine kinase; genes, reporter; rats; high performance liquid chromatography; fluorine 18; pet; thymidine kinase 1; herpes simplex virus 1; hydrolysis; heart; intestine; hsv1-tk; toluenesulfonic acid derivative; staining and labeling; radiochemistry; viral proteins; 18f; purification; virus enzyme; sulfone derivative; 2′-fluoro-2′-deoxy-1-β-d-arabinofuranosyl-5-(2- fluoroethyl)-uracil; 2' fluoro 2' deoxy 5 fluoroethyl 1 beta dextro arabinofuraosyluracil f 18 |
| Journal Title: | Nuclear Medicine and Biology |
| Volume: | 32 |
| Issue: | 8 |
| ISSN: | 0969-8051 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2005-11-01 |
| Start Page: | 811 |
| End Page: | 819 |
| Language: | English |
| DOI: | 10.1016/j.nucmedbio.2005.07.007 |
| PUBMED: | 16253805 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 15" - "Export Date: 24 October 2012" - "CODEN: NMBIE" - "Source: Scopus" |
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